title: Neurotoxicity of sedative and analgesia drugs in young infants with congenital heart disease: 4-year follow-up.
abstract: OBJECTIVE
  To determine whether sedation/analgesia drugs used before, during, and after infant cardiac surgery are associated with neurocognitive and functional outcomes.
  
  
  BACKGROUND
  Some animal models suggest neurotoxic effects of anesthetic drugs on the developing brain; however, potential human effects are unknown. Whether these results can be extrapolated to humans is unknown.
  
  
  METHODS
  Prospective follow-up project of all infants ≤6 weeks old having surgery for congenital heart disease between 04/03 and 12/06. Demographic, perioperative, and sedation/analgesia variables were collected. Outcomes at kindergarten age were Wechsler Preschool and Primary Scale of Intelligence-III, Beery-Buktenica Developmental Test of Visual Motor Integration (VMI-V), and General Adaptive Composite (GAC) of the Adaptive Behavior Assessment System-II. Multivariable linear regression was used to identify predictor variables.
  
  
  RESULTS
  From 135 infants who underwent heart surgery, 19 died, 17 were excluded, 8 were lost to follow-up, leaving 91 children for analysis. Multiple linear regression found days on chloral hydrate [3.5 (3.7) days] was associated with lower performance intelligence quotient (PIQ) (Effect size -1.03; 95% CI -1.96, -0.10; P = 0.03), and cumulative dose [54.2 (60.3) mg·kg(-1) ] of benzodiazepines was associated with lower VMI scores (Effect size -0.07; 95% CI -0.12, -0.01; P = 0.026). No other associations were found between sedation/analgesia variables and full-scale IQ, PIQ, Verbal IQ, VMI, or GAC.
  
  
  CONCLUSIONS
  Assessment of this cohort at kindergarten age found a small statistically significant association between days on chloral hydrate and PIQ, and benzodiazepine cumulative dose and lower VMI. No other association between sedation/analgesia drugs and outcomes was found.
authors.affiliation: Department of Pediatrics, University of Alberta, Edmonton, AB, Canada.
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Garcia Guerra
authors.forename: Charlene M T
authors.initials: CM
authors.lastname: Robertson
authors.forename: Gwen Y
authors.initials: GY
authors.lastname: Alton
authors.forename: Ari R
authors.initials: AR
authors.lastname: Joffe
authors.forename: Dominic A
authors.initials: DA
authors.lastname: Cave
authors.forename: Farzana
authors.initials: F
authors.lastname: Yasmin
authors.forename: Irina A
authors.initials: IA
authors.lastname: Dinu
authors.forename: Dianne E
authors.initials: DE
authors.lastname: Creighton
authors.forename: David B
authors.initials: DB
authors.lastname: Ross
authors.forename: Ivan M
authors.initials: IM
authors.lastname: Rebeyka
mesh_terms: D000700:Analgesics / Q000009:adverse effects*; D002675:Child, Preschool; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006330:Heart Defects, Congenital / Q000150:complications* / Q000601:surgery; D006801:Humans; D006993:Hypnotics and Sedatives / Q000009:adverse effects*; D007223:Infant; D007231:Infant, Newborn; D007360:Intelligence / Q000187:drug effects; D007361:Intelligence Tests; D016014:Linear Models; D008297:Male; D020258:Neurotoxicity Syndromes / Q000523:psychology*; D011446:Prospective Studies; D016896:Treatment Outcome; D014888:Wechsler Scales
chemical_list: D000700:Analgesics; D006993:Hypnotics and Sedatives
keywords: analgesia; congenital heart disease; neonates; neurotoxicity; outcomes; sedation